Statement from FDA Commissioner Scott Gottlieb, M.D., on new FDA efforts to support more efficient development of targeted therapies

In recent years, the medical community has experienced a shift in the way health care is practiced. Rather than focusing solely on how to treat an overall disease type, medical innovators are now exploring how to tailor treatments that target unique characteristics of an individual’s disease, such as the genetic profile of a person's tumor. Innovation in this modern, targeted approach to medicine has already led to new more targeted medicines and, in some cases, therapies that are tailored to individual patients.

The FDA has an important role to play in advancing this targeted approach to treating disease by building a modern framework that ensures we’re providing the guidance and resources needed to efficiently develop these novel products using new technology. In particular, the FDA needs to clarify and expand an existing pathway that allows innovators to develop products based on the molecular markers that the drug targets, rather than the more traditional approach to drug development, where new medicines were developed based on the disease phenotype that they targeted. In many cases, science is revealing that the driver of disease is really a molecular change in the body. New drugs are being developed based solely on their ability to target these underlying molecular subtypes. Moreover, this same molecular change may be present as the driving factor of many different disease phenotypes. When drugs successfully target these molecular mistakes to reverse the effects of different diseases, we need a development pathway that allows the new drug to pursue approval in each of these novel settings on the basis of the molecular marker that the drug targets. In the setting of oncology, this is often referred to as tissue agnostic drug development.

By providing clear guidance on the regulatory and scientific frameworks for product developers, safe and effective targeted treatments can be identified with scientifically valid tests and ultimately, made available to patients faster. That’s why today we are issuing two draft guidances that will provide medical product developers with greater clarity on the FDA’s recommendations for researching and developing the next generation of individualized therapies.

The first draft guidance, “Developing Targeted Therapies in Low-Frequency Molecular Subsets of a Disease,” addresses the important topic of finding treatments that address the underlying molecular changes (e.g., genetic mutations) that often cause or contribute to diseases, including uncommon molecular changes that are present in a small subset of patients. This draft guidance (which is also in a more concise, streamlined format) proposes an approach for drug developers to enroll patients based on the identification of rare mutations into clinical trials for targeted therapies when reasonable scientific evidence suggests the drug could be effective in patients with these genomic findings. The guidance discusses the evidence needed to demonstrate effectiveness for a variety of molecular subsets within a particular disease, which could lead to more consistent development and approval of targeted therapies for patients who are likely to benefit from them. These scientific principles described in the guidance could also be applied to supporting “tissue agnostic” drug development. This relates to how drugs may be able to gain regulatory approval on the basis of targeting a molecular subtype that is common across different phenotypes, rather than solely on the individual disease states. We think both approaches have the potential to increase the likelihood of finding viable treatment options for those with less common mutations. When finalized, this draft guidance will represent the FDA’s current thinking. The FDA also plans to publish a manuscript early next year that provides a detailed, comprehensive look at this issue.

The second draft guidance, “Investigational IVD Devices Used in Clinical Investigations of Therapeutic Products,” seeks to provide those running clinical trials with a clear framework to reference when determining if an in vitro diagnostic (IVD) device used in a therapeutic product study must undergo its own FDA review, distinct from the drug being studied. To develop new targeted therapies that are safe and effective, clinical trials often use investigational, or unapproved, IVDs to assess biomarkers and guide the selection of therapeutic products or care strategies that are applied to study participants.

When final, this draft guidance will clarify the appropriate regulatory pathway for investigational IVDs used in clinical trials for therapeutic products, which is significant so that trial results for a novel targeted therapy are not undermined just because the diagnostic test to determine a specific biomarker did not meet appropriate regulatory criteria. The aim is to make the process for developing more targeted “drug and diagnostics systems” more efficient and to simplify the proper development of these approaches.

Building on the IVD draft guidance issued today, we are also considering ways to streamline the review of oncology therapeutic products and the IVDs used with these products, and plan to issue draft guidance on this in the near future. The goal is to reduce the burden on sponsors for the development of certain cancer drugs, and on FDA staff as well.

These draft guidances are just a few examples of the FDA’s ongoing efforts to advance the development of innovative, targeted drugs and foster the availability of individualized treatment approaches. For example, earlier this month, the FDA issued draft guidance that describes a potential new approach for companies to collaborate and test multiple drug products in the same clinical trials for rare pediatric diseases, thereby reducing the number of patients treated with placebo. We also outlined how modeling and simulation can be used to reduce the reliance on placebo arms in these rare pediatric settings. Finally, we specifically addressed a more efficient pathway for developing drugs targeted to the rare pediatric disorder Gaucher Disease. We also recently authorized three, novel next generation sequencing-based devices for the detection of multiple cancer markers with the run of a single test – enabling the development of evidence to drive more individualized care management decisions.

By proposing streamlined approaches for our colleagues in the research and development communities, the FDA hopes to enable more efficient access to safe and effective, novel targeted therapies for the patients who need them. We look forward to receiving feedback on the draft guidances issued today and remain committed to assisting the medical community as it further modernizes and individualizes approaches to care, to increase the public health benefit offered by new medical technologies.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.